This application responds to RFA-CA-09-001, which requests applications for Centers for Population Health and Health Disparities (CPHHD) that will collaborate with other such Centers to promote transdisciplinary research in health disparities. In this application, the University of Washington (UW) and Black Hills Center for American Indian Health (BHCAIH) seek support for a Center for Native Population Health Disparities (CNPHD). Our aim is to directly contribute to improved cancer health outcomes and quality of life for American Indian/Alaska Native (AI/AN) populations - populations that are experiencing dramatic health inequities. Although strides have been made in improving health and life expectancy in Native communities, much work remains, as eloquently argued in the Institute of Medicine report, Examining the Heath Disparities Research Plan of the National Institutes of Health: Unfinished Business'^ and the Surgeon General's report. Mental Health: Culture, Race, and Ethnicity.^ Our CNPHD will strive to address the gaps identified in these seminal publications. Our research agenda articulates a model for AI/AN health and health disparities that is well-grounded in current theory, consistent with that of the CPHHDs, and applicable to all our projects. The many Native people involved in this Center, as well as our Community Action Board and 2 AI/AN sociologists, will help us critically examine the role of culture in the model. Our investigations reiterate a single leitmotif - the examination of genetic, environmental, biological, psychosocial, and cultural influences on cancer health disparities at multiple levels and across the lifespan. Our projects include children, youth, and adults. The proposed CNPHD will fill a striking research gap, since none of the 8 currently funded CPHHDs examines AI/AN health disparities and only 1 targets rural populations. Our Center will truly represent our research partner communities, with 11 AI/ANs serving in Icey roles, for example as Project and Core Leaders or Co-investigators (see Table 5 at end). Most notably, the Co-Principal Investigator is an enrolled member of the Cheyenne River Sioux Tribe and directs a community-based organization. As a result, all proposed projects have deep and meaningful ties to their respective communities. The unique connection between our investigators and the tribal communities imbues our work with a special dynamic. Investigators are more fully invested in the communities with which they work, and this commitment goes a long way to ensuring reciprocity and respect among ail parties involved in the research. Finally, the CNPHD will truly be transdisciplinary. We bring together scholars from across the full spectrum of biological, social, and behavioral sciences. Of special note, we do not limit team science to traditional academic circles, but bring in ideas and Native expertise from community-based leaders and entities. We envision that this approach will eventually move research on AI/AN health disparities beyond the purely descriptive into meaningful action. The CNPHD will pursue an integrated, multi-faceted research program that capitalizes on several large, well-organized, existing efforts and databases, as well as numerous well-established and mutually respectful relationships, to address issues in the genetics, etiology, epidemiology, primary and secondary prevention, clinical assessment, treatment, and survivorship of cancer. Clinical, basic, and social sciences are linked with a community-based participatory perspective to provide a transdisciplinary research program of the highest scientific and programmatic caliber for AI/AN community members, patients, clinicians, researchers, and health decision-makers. Notably, this application follows the overarching requirements for CPHHDs to 1) include scientists from basic, clinical, and social sciences; 2) focus on an underserved population; 3) incorporate principles of community-based participatory research; 4) include interventions directed towards at least 2 levels; 5) offer career development opportunities; and 6) interact and harmonize with other CPHHDs and NIH program staff to conduct transdisciplinary, multi-site, highly interactive research.